RESUMEN
Vitamin D is mainly produced in the skin (cholecalciferol) by sun exposure while a fraction of it is obtained from dietary sources (ergocalciferol). Vitamin D is further processed to 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D (calcitriol) in the liver and kidneys, respectively. Calcitriol is the active form which mediates the actions of vitamin D via vitamin D receptor (VDR) which is present ubiquitously. Defect at any level in this pathway leads to vitamin D deficient or resistant rickets. Nutritional vitamin D deficiency is the leading cause of rickets and osteomalacia worldwide and responds well to vitamin D supplementation. Inherited disorders of vitamin D metabolism (vitamin D-dependent rickets, VDDR) account for a small proportion of calcipenic rickets/osteomalacia. Defective 1α hydroxylation of vitamin D, 25 hydroxylation of vitamin D, and vitamin D receptor result in VDDR1A, VDDR1B and VDDR2A, respectively whereas defective binding of vitamin D to vitamin D response element due to overexpression of heterogeneous nuclear ribonucleoprotein and accelerated vitamin D metabolism cause VDDR2B and VDDR3, respectively. Impaired dietary calcium absorption and consequent calcium deficiency increases parathyroid hormone in these disorders resulting in phosphaturia and hypophosphatemia. Hypophosphatemia is a common feature of all these disorders, though not a sine-qua-non and leads to hypomineralisation of the bone and myopathy. Improvement in hypophosphatemia is one of the earliest markers of response to vitamin D supplementation in nutritional rickets/osteomalacia and the lack of such a response should prompt evaluation for inherited forms of rickets/osteomalacia.
Asunto(s)
Raquitismo Hipofosfatémico Familiar , Osteomalacia , Raquitismo , Deficiencia de Vitamina D , Humanos , Calcitriol , Receptores de Calcitriol , Osteomalacia/tratamiento farmacológico , Osteomalacia/etiología , Osteomalacia/metabolismo , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/tratamiento farmacológico , Raquitismo/tratamiento farmacológico , Raquitismo/etiología , Vitamina D/uso terapéutico , Vitamina D/metabolismo , VitaminasRESUMEN
INTRODUCTION: Vitamin D deficiency affects from 10% to 50% in various pediatric population groups and causes life-threatening hypocalcemia in infants, crippling rickets in infants and children, and increased risk of subsequent adult metabolic and neurologic problems. AREAS COVERED: An English language literature search of PubMed was performed since 1940 as were the authors' personal literature collections. References identified in the reviewed literature are considered. DIAGNOSIS: The diagnosis of vitamin D deficiency is based on serum 25-hydroxyvitamin D levels. Clinical features of rickets include bone deformities and elevated alkaline phosphatase. Most children and adolescents who are biochemically vitamin D deficient do not have specific symptoms or signs of deficiency. PREVENTION: Prevention of vitamin D deficiency is via exposure to sunshine, food and beverage fortification, and dietary supplementation. TREATMENT: Effective treatment of vitamin D deficiency is via oral or injectable administration of vitamin D. Dosing and duration of vitamin D therapy have been described for healthy children and for children with underlying medical conditions, but recommendations vary. EXPERT OPINION: Further investigation is needed to determine long-term non-skeletal effects of childhood vitamin D deficiency, benefits of supplementation in asymptomatic individuals with biochemical vitamin D deficiency, and appropriate screening for vitamin D deficiency in asymptomatic children and adolescents.
Asunto(s)
Hipocalcemia , Raquitismo , Deficiencia de Vitamina D , Lactante , Adolescente , Niño , Humanos , Deficiencia de Vitamina D/tratamiento farmacológico , Raquitismo/diagnóstico , Raquitismo/tratamiento farmacológico , Raquitismo/etiología , Vitamina D/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVES: A 14-week-old female domestic longhair kitten presented with shifting lameness and disproportionately smaller size compared with a co-housed littermate. METHODS: Hematology and serum biochemical testing were conducted to investigate causes for delayed growth, and radiographs of the appendicular skeleton were obtained. RESULTS: The afflicted kitten had marked hypocalcemia, mild hypophosphatemia and substantial elevations in alkaline phosphatase activity, as well as pathognomonic radiographic findings consistent with rickets. Skeletal changes and hypocalcemia prompted testing of concentrations of parathyroid hormone (PTH) and vitamin D metabolites. Endocrine testing demonstrated significant increases in serum concentrations of PTH and 1,25-dihydroxycholecalciferol (calcitriol), supporting a diagnosis of vitamin D-dependent rickets type 2. Provision of analgesia, supraphysiologic doses of calcitriol and calcium carbonate supplementation achieved normalization of the serum calcium concentration and restoration of normal growth, although some skeletal abnormalities persisted. Once skeletally mature, ongoing calcitriol supplementation was not required. Whole-exome sequencing (WES) was conducted to identify the underlying DNA variant. A cytosine deletion at cat chromosome position B4:76777621 in VDR (ENSFCAT00000029466:c.106delC) was identified and predicted to cause a stop codon in exon 2 (p.Arg36Glufs*18), disrupting >90% of the receptor. The variant was unique and homozygous in this patient and absent in the sibling and approximately 400 other cats for which whole-genome and whole-exome data were available. CONCLUSIONS AND RELEVANCE: A unique, heritable form of rickets was diagnosed in a domestic longhair cat. WES identified a novel frameshift mutation affecting the gene coding for the vitamin D3 receptor, determining the likely causal genetic variant. Precision medicine techniques, including whole-exome and whole-genome sequencing, can be a standard of care in cats to identify disease etiologies, and to target therapeutics and personalize treatment.
Asunto(s)
Enfermedades de los Gatos , Hipocalcemia , Raquitismo , Femenino , Gatos , Animales , Medicina de Precisión/veterinaria , Secuenciación del Exoma/veterinaria , Calcitriol , Hipocalcemia/veterinaria , Mutación del Sistema de Lectura , Raquitismo/diagnóstico , Raquitismo/tratamiento farmacológico , Raquitismo/genética , Raquitismo/veterinaria , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Gatos/genéticaRESUMEN
Bowing of the legs is common in childhood. Most times it is considered to be rickets without considering other possibilities. Blount´s disease is a close differential diagnosis which is developmental deformity characterized by intorsion of tibia leading to varus angulation. This case report aims to encourage pediatricians to expand their vision and consider other possibilities when a case of bowing of legs is encountered. Here we report a case of a four-year-old boy with bowing of both legs noticed first at 2.5 years of age. There was no history suggestive of trauma. Development of the child was age appropriate in all domains. He was receiving treatment for rickets for 1.5 years in form of oral vitamin D3 and calcium supplementations. He had no other clinical signs of rickets like frontal bossing, widening of wrists, and rachitic rosary except bowing of legs. His biochemical parameters did not show any alterations that would support the diagnosis of rickets. Weight-bearing radiographs of lower limbs showed medial intorsion of bilateral tibia with metaphyseo-diaphysial angle to be 25º on the right side and 20º on the left side, which was beyond the physiological normal angulation, therefore he was diagnosed as a case of Blount´s disease, stage III as per Langenskiöld classification. All the bow legs is not always rickets in pediatric practice. Therefore, various differential diagnoses should be kept in mind as early diagnosis and intervention can change a child´s life.
Asunto(s)
Genu Varum , Raquitismo , Enfermedades del Desarrollo Óseo , Calcio , Niño , Preescolar , Colecalciferol , Genu Varum/complicaciones , Humanos , Masculino , Osteocondrosis/congénito , Raquitismo/diagnóstico , Raquitismo/tratamiento farmacológico , Raquitismo/etiología , TibiaRESUMEN
OBJECTIVES: Children with epilepsy are at increased risk of vitamin D deficiency. We aimed to compare the effect of two ergocalciferol regimens given for 90 days. METHODS: Epileptic patients aged 5-18 years who received at least one antiepileptic drug (AED) for more than 6 months and had serum 25-OHD <30 ng/mL were randomized to receive 20,000 IU/10 d (standard dose, n=41) or 60,000 IU/10 d (high dose, n=41) of oral ergocalciferol. Serum Ca, P, Mg, ALP, iPTH and urine Ca/Cr ratio were measured at baseline and after 90 days of treatment. Change in serum 25-OHD and vitamin D status after treatment was evaluated. RESULTS: The initial serum 25-OHD in the standard dose and high dose group was 19.5 ± 4.9 and 18.4 ± 4.6 ng/mL, respectively. Serum 25-OHD after treatment was significantly higher in the high dose group (39.0 ± 11.5 vs. 27.5 ± 8.6 ng/mL, p<0.05). The average increase in serum 25-OHD in the high dose and standard dose group was 20.6 ± 11.4 and 7.2 ± 7.5 ng/mL, respectively (p<0.05). Normalized serum 25-OHD was achieved in 80.5% of the high dose group compared to 36.6% of the standard dose group (p<0.05). No adverse events were found. Patients with a BMI Z-score>0 had a 2.5 times greater risk of continued hypovitaminosis D after treatment compared to those with a BMI Z-score<0 (95% CI: 1.0-5.9, p<0.05). CONCLUSIONS: Oral ergocalciferol 60,000 IU/10 d for 90 days was more effective at normalizing serum 25-OHD than 20,000 IU/10 d in epileptic children and adolescents who were receiving AEDs.
Asunto(s)
Epilepsia , Raquitismo , Deficiencia de Vitamina D , Niño , Humanos , Adolescente , Vitamina D , Raquitismo/tratamiento farmacológico , Vitaminas/uso terapéutico , Ergocalciferoles/uso terapéuticoRESUMEN
We investigated the effect of hypocalcemia on plasma renin, aldosterone, and urine PGE2 levels in children with vitamin D deficiency rickets (VDDR). In the study group, 25 patients with VDDR-induced hypocalcemia were treated with a single dose of 150,000-300,000 IU cholecalciferol and 50 mg/kg/day elemental Ca for 10 days. On any day between 21th and 30th days after the treatment, the patients' clinical, biochemical and radiologic findings were re-evaluated. The healthy children with the same sex and similar age as the study group comprised the control group. Plasma sodium (Na), potassium (K), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), parathyroid hormone (PTH), 25- hydroxy vitamin D (25OHD), renin, aldosterone; and urinary Ca, creatinine (Cr) and prostaglandin E2 (PGE2) levels were measured in both the study (pre-treatment and post-treatment) and the control group. Plasma Ca, P, 25OHD and renin levels and urinary PGE2/Cr ratio in the post-treatment group were significantly higher than those in the pre-treatment group while K, ALP, and PTH concentrations were significantly lower. Plasma ALP and PTH levels in pre-treatment group were significantly higher than in the control group while Ca, P, 25OHD, aldosterone and renin concentrations and urinary PGE2/Cr ratio were significantly lower. Post-treatment plasma Ca level was significantly decreased in normal limits compared to the control group while other biochemical parameters were not different from the control group. Plasma Ca concentration was positively correlated with renin level and urinary PGE2/Cr ratio. The findings suggest that hypocalcemia may inhibit the production of renin, aldosterone and PGE2 and a blunt aldosterone secretion may develop even after recovery from hypocalcemia.
Asunto(s)
Hipocalcemia , Raquitismo , Deficiencia de Vitamina D , Aldosterona/uso terapéutico , Fosfatasa Alcalina/uso terapéutico , Calcio/uso terapéutico , Calcio/orina , Niño , Colecalciferol/uso terapéutico , Creatinina/uso terapéutico , Dinoprostona/uso terapéutico , Humanos , Hipocalcemia/tratamiento farmacológico , Hormona Paratiroidea/uso terapéutico , Fósforo/uso terapéutico , Potasio/uso terapéutico , Prostaglandinas E/uso terapéutico , Prostaglandinas E/orina , Renina/uso terapéutico , Raquitismo/tratamiento farmacológico , Sodio , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/tratamiento farmacológicoRESUMEN
Vitamin D has a well-known role in the calcium homeostasis associated with the maintenance of healthy bones. It increases the efficiency of the intestinal absorption of dietary calcium, reduces calcium losses in urine, and mobilizes calcium stored in the skeleton. However, vitamin D receptors are present ubiquitously in the human body and indeed, vitamin D has a plethora of non-calcemic functions. In contrast to most vitamins, sufficient vitamin D can be synthesized in human skin. However, its production can be markedly decreased due to factors such as clothing, sunscreens, intentional avoidance of the direct sunlight, or the high latitude of the residence. Indeed, more than one billion people worldwide are vitamin D deficient, and the deficiency is frequently undiagnosed. The chronic deficiency is not only associated with rickets/osteomalacia/osteoporosis but it is also linked to a higher risk of hypertension, type 1 diabetes, multiple sclerosis, or cancer. Supplementation of vitamin D may be hence beneficial, but the intake of vitamin D should be under the supervision of health professionals because overdosing leads to intoxication with severe health consequences. For monitoring vitamin D, several analytical methods are employed, and their advantages and disadvantages are discussed in detail in this review.
Asunto(s)
Raquitismo , Deficiencia de Vitamina D , Humanos , Vitamina D/metabolismo , Vitamina D/uso terapéutico , Calcio , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/tratamiento farmacológico , Vitaminas , Raquitismo/complicaciones , Raquitismo/tratamiento farmacológico , Calcio de la DietaRESUMEN
Here, we discuss the management of different forms of rickets, including new therapeutic approaches based on recent guidelines. Management includes close monitoring of growth, the degree of leg bowing, bone pain, serum phosphate, calcium, alkaline phosphatase as a surrogate marker of osteoblast activity and thus degree of rickets, parathyroid hormone, 25-hydroxyvitamin D3, and calciuria. An adequate calcium intake and normal 25-hydroxyvitamin D3 levels should be assured in all patients. Children with calcipenic rickets require the supplementation or pharmacological treatment with native or active vitamin D depending on the underlying pathophysiology. Treatment of phosphopenic rickets depends on the underlying pathophysiology. Fibroblast-growth factor 23 (FGF23)-associated hypophosphatemic rickets was historically treated with frequent doses of oral phosphate salts in combination with active vitamin D, whereas tumor-induced osteomalacia (TIO) should primarily undergo tumor resection, if possible. Burosumab, a fully humanized FGF23-antibody, was recently approved for treatment of X-linked hypophosphatemia (XLH) and TIO and shown to be superior for treatment of XLH compared to conventional treatment. Forms of hypophosphatemic rickets independent of FGF23 due to genetic defects of renal tubular phosphate reabsorption are treated with oral phosphate only, since they are associated with excessive 1,25-dihydroxyvitamin D production. Finally, forms of hypophosphatemic rickets caused by Fanconi syndrome, such as nephropathic cystinosis and Dent disease require disease-specific treatment in addition to phosphate supplements and active vitamin D. Adjustment of medication should be done with consideration of treatment-associated side effects, including diarrhea, gastrointestinal discomfort, hypercalciuria, secondary hyperparathyroidism, and development of nephrocalcinosis or nephrolithiasis.
Asunto(s)
Raquitismo Hipofosfatémico Familiar , Síndrome de Fanconi , Raquitismo Hipofosfatémico , Raquitismo , Calcio/uso terapéutico , Niño , Raquitismo Hipofosfatémico Familiar/tratamiento farmacológico , Raquitismo Hipofosfatémico Familiar/genética , Factores de Crecimiento de Fibroblastos , Humanos , Osteomalacia , Síndromes Paraneoplásicos , Fosfatos , Raquitismo/tratamiento farmacológico , Raquitismo/etiología , Raquitismo Hipofosfatémico/tratamiento farmacológico , Raquitismo Hipofosfatémico/etiología , Vitamina D/uso terapéuticoRESUMEN
Vitamin D supplementation can prevent and cure nutritional rickets in infants and children. Preclinical and observational data suggest that the vitamin D endocrine system has a wide spectrum of skeletal and extra-skeletal activities. There is consensus that severe vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) concentration <30 nmol/l) should be corrected, whereas most guidelines recommend serum 25OHD concentrations of >50 nmol/l for optimal bone health in older adults. However, the causal link between vitamin D and many extra-skeletal outcomes remains unclear. The VITAL, ViDA and D2d randomized clinical trials (combined number of participants >30,000) indicated that vitamin D supplementation of vitamin D-replete adults (baseline serum 25OHD >50 nmol/l) does not prevent cancer, cardiovascular events, falls or progression to type 2 diabetes mellitus. Post hoc analysis has suggested some extra-skeletal benefits for individuals with vitamin D deficiency. Over 60 Mendelian randomization studies, designed to minimize bias from confounding, have evaluated the consequences of lifelong genetically lowered serum 25OHD concentrations on various outcomes and most studies have found null effects. Four Mendelian randomization studies found an increased risk of multiple sclerosis in individuals with genetically lowered serum 25OHD concentrations. In conclusion, supplementation of vitamin D-replete individuals does not provide demonstrable health benefits. This conclusion does not contradict older guidelines that severe vitamin D deficiency should be prevented or corrected.
Asunto(s)
Diabetes Mellitus Tipo 2 , Raquitismo , Deficiencia de Vitamina D , Anciano , Niño , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Suplementos Dietéticos , Humanos , Lactante , Raquitismo/inducido químicamente , Raquitismo/tratamiento farmacológico , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/tratamiento farmacológicoRESUMEN
JUSTIFICATION: The emerging literature on prevalence of vitamin D deficiency in India, prevention and treatment strategies of rickets, and extra-skeletal benefits of vitamin D suggest the need for revising the existing guidelines for prevention and treatment of vitamin D deficiency in India. OBJECTIVES: To review the emerging literature on vitamin D prevalence and need for universal vitamin D supplementation. To suggest optimum vitamin D therapy for treatment of asymptomatic and symptomatic vitamin D deficiency, and rickets. To evaluate the extra-skeletal health benefits of vitamin D in children. PROCESS: A National consultative committee was formed that comprised of clinicians, epidemiologists, endocrinologists, and nutritionists. The Committee conducted deliberations on different aspects of vitamin D deficiency and rickets through ten online meetings between March and September, 2021. A draft guideline was formulated, which was reviewed and approved by all Committee members. RECOMMENDATIONS: The group reiterates the serum 25-hydroxy vitamin D cutoffs proposed for vitamin D deficiency, insufficiency, and sufficiency as <12 ng/mL, 12-20 ng/mL and >20 ng/mL, respectively. Vitamin D toxicity is defined as serum 25OHD >100 ng/mL with hypercalcemia and/or hypercalciuria. Vitamin D supplementation in doses of 400 IU/day is recommended during infancy; however, the estimated average requirement in older children and adolescents (400-600 IU/day, respectively) should be met from diet and natural sources like sunlight. Rickets and vitamin D deficiency should be treated with oral cholecalciferol, preferably in a daily dosing schedule (2000 IU below 1 year of age and 3000 IU in older children) for 12 weeks. If compliance to daily dosing cannot be ensured, intermittent regimens may be prescribed for children above 6 months of age. Universal vitamin D supplementation is not recommended in childhood pneumonia, diarrhea, tuberculosis, HIV and non-infectious conditions like asthma, atopic dermatitis, and developmental disorders. Serum 25-hydroxy vitamin D level of >20 ng/mL should be maintained in children with conditions at high-risk for vitamin deficiency, like nephrotic syndrome, chronic liver disease, chronic renal failure, and intake of anticonvulsants or glucocorticoids.
Asunto(s)
Pediatría , Raquitismo , Deficiencia de Vitamina D , Adolescente , Niño , Colecalciferol/uso terapéutico , Suplementos Dietéticos , Humanos , Raquitismo/tratamiento farmacológico , Raquitismo/prevención & control , Vitamina D , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/prevención & control , Vitaminas/uso terapéuticoRESUMEN
We have developed an in vitro system to easily examine the affinity for vitamin D receptor (VDR) and CYP24A1-mediated metabolism as two methods of assessing vitamin D derivatives. Vitamin D derivatives with high VDR affinity and resistance to CYP24A1-mediated metabolism could be good therapeutic agents. This system can effectively select vitamin D derivatives with these useful properties. We have also developed an in vivo system including a Cyp27b1-gene-deficient rat (a type I rickets model), a Vdr-gene-deficient rat (a type II rickets model), and a rat with a mutant Vdr (R270L) (another type II rickets model) using a genome editing method. For Cyp27b1-gene-deficient and Vdr mutant (R270L) rats, amelioration of rickets symptoms can be used as an index of the efficacy of vitamin D derivatives. Vdr-gene-deficient rats can be used to assess the activities of vitamin D derivatives specialized for actions not mediated by VDR. One of our original vitamin D derivatives, which displays high affinity VDR binding and resistance to CYP24A1-dependent metabolism, has shown good therapeutic effects in Vdr (R270L) rats, although further analysis is needed.
Asunto(s)
Descubrimiento de Drogas , Vitamina D , Animales , Evaluación Preclínica de Medicamentos , Humanos , Ratas , Raquitismo/tratamiento farmacológico , Raquitismo/genética , Raquitismo/metabolismo , Vitamina D/análogos & derivados , Vitamina D/farmacocinética , Vitamina D/uso terapéuticoRESUMEN
BACKGROUND: Severe prolonged vitamin D deficiency can cause rickets or osteomalacia. Both can be prevented by sunshine exposure or vitamin D supplementation. Although New Zealand guidance does not recommend vitamin D supplementation for the general population, it can be considered for individuals at risk of vitamin D deficiency. Routine measurement of 25-hydroxyvitamin D (25OHD) is also considered unnecessary. METHODS: We investigated the rates of vitamin D supplementation, rickets and osteomalacia in New Zealand, and of 25OHD results in Auckland, over the last two decades. RESULTS: Vitamin D prescriptions increased 14-fold, from 86,295/year to 1,215,507/year, between 2003 and 2019, with medication costs alone in 2019 being >$1 million. Despite these changes, the annual prevalence of hospital admissions for rickets, osteomalacia and unspecified vitamin D deficiency remained low and stable (10-20/year). 25OHD concentrations increased between 2002 and 2003 and between 2009 and 2019, and in the later time-period, 25OHD tests mainly identified individuals without vitamin D deficiency (40-50% >75nmol/L, 65-70% >50nmol/L and only 7-12.5% <25nmol/L). CONCLUSIONS: Osteomalacia and rickets persist at low rates despite widespread, increasingly costly vitamin D supplementation and testing, which largely identifies individuals without vitamin D deficiency. These results suggest that vitamin D guidance and practice in New Zealand should change.
Asunto(s)
Colecalciferol/uso terapéutico , Osteomalacia/tratamiento farmacológico , Raquitismo/tratamiento farmacológico , Deficiencia de Vitamina D/tratamiento farmacológico , Vitaminas/uso terapéutico , Análisis Químico de la Sangre , Suplementos Dietéticos , Humanos , Nueva Zelanda/epidemiología , Osteomalacia/epidemiología , Osteomalacia/prevención & control , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/estadística & datos numéricos , Prevalencia , Raquitismo/epidemiología , Raquitismo/prevención & control , Medición de Riesgo , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/prevención & controlRESUMEN
Rickets is an often-neglected, painful, and disabling childhood condition of impaired bone mineralization. In this case series we describe a cluster of 29 children with severe, painful bone deformities who live in the very remote region of Nagaland in northwest Myanmar. Children were found to have low 25-hydroxyvitamin D, elevated parathyroid hormone, and elevated alkaline phosphatase levels, consistent with nutritional rickets secondary to vitamin D deficiency, calcium deficiency, or a combination of the two. After treatment with vitamin D3 and calcium carbonate, significant improvement was seen in symptoms, biochemistry, and radiography. This is the first report of nutritional rickets in Myanmar in more than 120 years. Vitamin D and calcium supplementation, and food fortification for pregnant women and young children may be required to prevent this potentially devastating disease.
Asunto(s)
Calcio/deficiencia , Calcio/uso terapéutico , Raquitismo/diagnóstico , Raquitismo/tratamiento farmacológico , Deficiencia de Vitamina D/complicaciones , Vitamina D/uso terapéutico , Adolescente , Fosfatasa Alcalina/sangre , Niño , Preescolar , Femenino , Humanos , India/epidemiología , Masculino , Mianmar/epidemiología , Hormona Paratiroidea/sangre , Raquitismo/epidemiología , Raquitismo/etiología , Población Rural/estadística & datos numéricos , Resultado del Tratamiento , Vitamina D/análogos & derivados , Vitamina D/sangreRESUMEN
In 2016, a global consensus on the prevention, diagnosis and management of nutritional rickets was published. The bone and mineral working group of the Australasian Paediatric Endocrine Group provides a summary and highlights differences to previous Australian and New Zealand (ANZ) guidelines on vitamin D deficiency and their implications for clinicians. Key points are: (i) The International Consensus document is focused on nutritional rickets, whereas the ANZ guidelines were focused on vitamin D deficiency. (ii) Definitions for the interpretation of 25-hydroxy vitamin D (25OHD) levels do not differ between statements. (iii) The global consensus recommends that routine 25OHD screening should not be performed in healthy children and recommendations for vitamin D supplementation are not based solely on 25OHD levels. The Australasian Paediatric Endocrine Group bone and mineral working group supports that screening for vitamin D deficiency should be restricted to populations at risk. (iv) Recommendations from the global consensus for vitamin D dosages for the therapy of nutritional rickets (diagnosed based on history, physical examination, biochemical testing and a confirmation by X-rays) are higher than in ANZ publications. (v) The global consensus recommends the implementation of public health strategies such as universal supplementation with vitamin D from birth to 1 year of age and food fortification. We conclude that updated global recommendations for therapy of nutritional rickets complement previously published position statements for Australia and New Zealand. Screening, management and the implementation of public health strategies need to be further explored for Australia.
Asunto(s)
Raquitismo , Deficiencia de Vitamina D , Australia , Niño , Consenso , Humanos , Nueva Zelanda , Raquitismo/diagnóstico , Raquitismo/tratamiento farmacológico , Raquitismo/prevención & control , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/prevención & controlRESUMEN
RATIONALE: Currently, the relationship between heterozygous mutations in SLC34A1 and hypophosphatemia is controversial. Here we report an autosomal dominant hypophosphatemia pedigree carrying a novel heterozygous mutation in SLC34A1. PATIENT CONCERNS: The proband is a 32-year old young man, presented with progressive pain and weakness in his lower extremities for more than 5 years. The proband showed persistent hypophosphatemia and low TmPO4/GFR values, indicating renal phosphate leak. His grandfather, father, and one of his uncles showed the similar symptoms. DIAGNOSES: Autosomal dominant hypophosphatemia. INTERVENTIONS AND OUTCOMES: Phosphorus supplement was prescribed to the proband and his affected uncle. Both their serum phosphorus levels recovered to normal and their symptoms such as back pain and lower extremity weakness were completely relieved. Whole exome sequencing was performed to identify disease-causing mutations in proband. LESSONS: A novel heterozygous missense mutation c.680A>G (p. N227S) in exon 7 of SLC34A1 was found in proband by whole exome sequencing, which was also found in other 4 family members of this pedigree. Our report of an autosomal dominant hypophosphatemia pedigree with 5 mutant carriers enriches the clinical phenotype caused by the SLC34A1 mutations and further affirms the heterozygous mutations are causative for hypophosphatemia.
Asunto(s)
Raquitismo Hipofosfatémico Familiar/tratamiento farmacológico , Raquitismo Hipofosfatémico Familiar/genética , Fósforo/uso terapéutico , Raquitismo/tratamiento farmacológico , Raquitismo/genética , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo IIa/genética , Adulto , Raquitismo Hipofosfatémico Familiar/diagnóstico , Humanos , Masculino , Mutación Missense , Raquitismo/diagnósticoRESUMEN
We have reported that 25-hydroxyvitamin D3 [25(OH)D3] binds to vitamin D receptor and exhibits several biological functions directly in vitro. To evaluate the direct effect of 25(OH)D3 in vivo, we used Cyp27b1 knockout (KO) mice, which had no detectable plasma 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] when fed a diet containing normal Ca and vitamin D. Daily treatment with 25(OH)D3 at 250 µg kg-1 day-1 rescued rachitic phenotypes in the Cyp27b1 KO mice. Bone mineral density, female sexual cycles, and plasma levels of Ca, P, and PTH were all normalized following 25(OH)D3 administration. An elevated Cyp24a1 mRNA expression was observed in the kidneys, and plasma concentrations of Cyp24a1-dependent metabolites of 25(OH)D3 were increased. To our surprise, 1,25(OH)2D3 was detected at a normal level in the plasma of Cyp27b1 KO mice. The F1 to F4 generations of Cyp27b1 KO mice fed 25(OH)D3 showed normal growth, normal plasma levels of Ca, P, and parathyroid hormone, and normal bone mineral density. The curative effect of 25(OH)D3 was considered to depend on the de novo synthesis of 1,25(OH)2D3 in the Cyp27b1 KO mice. This suggests that another enzyme than Cyp27b1 is present for the 1,25(OH)2D3 synthesis. Interestingly, the liver mitochondrial fraction prepared from Cyp27b1 KO mice converted 25(OH)D3 to 1,25(OH)2D3. The most probable candidate is Cyp27a1. Our findings suggest that 25(OH)D3 may be useful for the treatment and prevention of osteoporosis for patients with chronic kidney disease.
Asunto(s)
25-Hidroxivitamina D3 1-alfa-Hidroxilasa/genética , Conservadores de la Densidad Ósea/farmacología , Calcifediol/farmacología , Calcitriol/biosíntesis , Calcitriol/sangre , Raquitismo/tratamiento farmacológico , Animales , Densidad Ósea/efectos de los fármacos , Calcitriol/genética , Calcio/sangre , Colestanotriol 26-Monooxigenasa/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Osteoporosis/tratamiento farmacológico , Hormona Paratiroidea/sangre , Fósforo/sangre , Vitamina D3 24-Hidroxilasa/biosíntesis , Vitamina D3 24-Hidroxilasa/genéticaRESUMEN
The etiology of endemic rickets was discovered a century ago. Vitamin D is the precursor of 25-hydroxyvitamin D and other metabolites, including 1,25(OH)2D, the ligand for the vitamin D receptor (VDR). The effects of the vitamin D endocrine system on bone and its growth plate are primarily indirect and mediated by its effect on intestinal calcium transport and serum calcium and phosphate homeostasis. Rickets and osteomalacia can be prevented by daily supplements of 400 IU of vitamin D. Vitamin D deficiency (serum 25-hydroxyvitamin D <50 nmol/L) accelerates bone turnover, bone loss, and osteoporotic fractures. These risks can be reduced by 800 IU of vitamin D together with an appropriate calcium intake, given to institutionalized or vitamin D-deficient elderly subjects. VDR and vitamin D metabolic enzymes are widely expressed. Numerous genetic, molecular, cellular, and animal studies strongly suggest that vitamin D signaling has many extraskeletal effects. These include regulation of cell proliferation, immune and muscle function, skin differentiation, and reproduction, as well as vascular and metabolic properties. From observational studies in human subjects, poor vitamin D status is associated with nearly all diseases predicted by these extraskeletal actions. Results of randomized controlled trials and Mendelian randomization studies are supportive of vitamin D supplementation in reducing the incidence of some diseases, but, globally, conclusions are mixed. These findings point to a need for continued ongoing and future basic and clinical studies to better define whether vitamin D status can be optimized to improve many aspects of human health. Vitamin D deficiency enhances the risk of osteoporotic fractures and is associated with many diseases. We review what is established and what is plausible regarding the health effects of vitamin D.
Asunto(s)
Huesos/metabolismo , Calcio/metabolismo , Vitamina D/metabolismo , Animales , Huesos/fisiología , Femenino , Humanos , Masculino , Osteomalacia/tratamiento farmacológico , Osteomalacia/prevención & control , Raquitismo/tratamiento farmacológico , Raquitismo/prevención & control , Transducción de Señal , Vitamina D/fisiología , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/prevención & controlRESUMEN
Vitamin D deficiency rickets is characterized by mineralization impairment in bone and cartilage of children caused by vitamin D deficiency in the body due to limited sunlight exposure and vitamin D intake. Vitamin D supplementation is recommended in developed countries. Low calcium intake is a risk factor for vitamin D deficiency rickets. For treatment, native vitamin D is used in developed countries, while active vitamin D is used in Japan.
Asunto(s)
Raquitismo/tratamiento farmacológico , Deficiencia de Vitamina D/tratamiento farmacológico , Vitamina D/uso terapéutico , Calcio de la Dieta/administración & dosificación , Niño , Humanos , OsteomalaciaRESUMEN
A variety of epidemiological studies and meta-analyses have shown that vitamin D insufficiency or deficiency not only affects bone and mineral metabolism, but is also linked to sarcopenia, metabolic diseases such as diabetes, obesity, and metabolic syndrome, cancer, autoimmune disease, and other diseases. There has been accumulating evidence that vitamin D deficiency, defined as a serum 25(OH)D value below 20 ng/mL, is a significant risk factor for each of these diseases. However, vitamin D supplementation has not shown a therapeutic effect in any of these diseases, and a detailed cause-and-effect relationship remains elusive. Future studies should consider non-skeletal effects when investigating cutoff levels of serum 25(OH)D for therapeutic intervention in vitamin D insufficiency and deficiency, the required supplement dose, and the length of supplementation.